Abstract

The liver is the major site of ethanol (ETOH) metabolism. Liver sinusoids contain lymphocytes with NK activity. The authors treated LEW rats for 2 weeks with i.p. injection of 1.25 ml 25% ETOH/kg 3 times/week and 5% ETOH in drinking water. Livers were perfused at 5-fold physiological pressure and cells obtained were banded on 1.077 density Ficoll. Their cytotoxicity was tested against {sup 51}Cr-labeled YAC-1 or U937 and compared to spleen and blood lymphocytes. In untreated rats, pit cell NK activity was 2-fold that of splenic lymphocytes and 4-fold that of blood lymphocytes. Compared to controls, ETOH-treated rats exhibited a 30 to 90% rise in pit cell NK activity detected with YAC-1 or U937 targets. The pit cell enhanced NK activity in ETOH-treated rats was further increased if polyinosinicpolycytidilic acid was injection i.p. 18 hours before the assay. Blood and spleen lymphocyte NK activity of ETOH-treated rats was also greater than in controls. There was no evidence that ETOH merely redistributed lymphocytes among the tissues. Although ETOH acutely inhibits NK activity in vitro, chronic ETOH increases in vivo.

The authors examined NK and OKT3 augmented NK activity in 14 IDDM patients and 15 age matched controls (28 +/- 6 vs 28.5 +/- 6 yrs respectively) to evaluate this aspect of antigen nonspecific immunity. NK and augmented NK function were examined at various target to effector cell ratios (E/T) using the K562 cell line (as target) in a 4 hr /sup 51/Cr release assay. Islet cell antibodies (ICA) were determined by standard methods. All of the diabetics (mean duration of disease 16 yrs) and controls were ICA (-). Their observations indicate that there is no significant difference between diabeticmore » and control subjects in NK activity. The ability of OKT3 to augment NK activity (by a T-cell mediated process) is also not significantly different between the two groups. An abnormal immune response to beta cells has a central role in the pathogenesis of IDDM. The nature of this autoimmune defect is unclear. The authors' present observations indicate that antigen nonspecific immune function may be normal in patients with IDDM. They propose that IDDM is a disease only of abnormal antigen specific immunoregulation.« less

A 5-year-old girl who was diagnosed as having erythrophagocytic lymphohistiocytosis died at age 9 years. Peripheral lymphocytes from the patient persistently lacked natural killer (NK) cell activity during the 4-year observation period: the percent lysis values as measured by a 4-hr /sup 51/Cr release assay at a 40:1 effector:target ratio were below 1.0% against K562 and Molt-4 cells as compared with the normal lymphocyte value (mean +/- SD) of 46.2% +/- 5.8% and 43.9% +/- 6.7%, respectively. The patient's lymphocytes never developed NK cell activity by their incubation with target cells for longer time periods or by their stimulation withmore » interferon-alpha, interleukin-2, or polyinosinic-polycytidilic acid. Single cell-in-agarose assay showed the absence of target-binding cells (TBCs): TBC numbers were below 0.3% as compared with the normal lymphocyte value of 8.1% +/- 1.3% (mean +/- SD). Flow cytometry showed a marked decrease in Leu-7+ cells (1.7%) and the absence of Leu-11+ cells (0.4%) in the peripheral blood. These results first demonstrate a case of erythrophagocytic lymphohistiocytosis in which there is the lack of NK cell activity due to the absence of circulating NK cells.« less

Mice that have been injected with /sup 89/Sr have fairly normal B and T cell function, but are abnormal in that they lack natural killer (NK) activity and other functions that require an intact bone marrow. These mice also have an increased potential for suppressor cell activity. We had previously shown that spleen cells from /sup 89/Sr-treated mice could transfer low NK activity and increased suppressor cell function to lethally irradiated syngeneic recipients. To investigate the mechanisms involved in perpetuating these defects, groups of normal spleen or bone marrow cells. Recipients were assayed for their NK activity and suppressor cellmore » function 5 to 14 wk later. it was found that the addition of normal cells in the donor inoculum resulted in normal NK activity. This indicates that low NK activity in /sup 89/Sr-treated mice was not due to the presence of a suppressor cell that prevented NK cell generation. It was additionally found that low NK activity in recipient mice could be boosted by interferon inducers. This would indicate that NK activity in the recipients was not due to a lack of interferon-sensitive pre-NK cells. Suppressor cell function in recipient mice depended on the type and number of normal cells in the donor inoculum. Bone marrow cells were very efficient in overcoming the tendency to produce suppressor cells. It took approximately 20 times more normal spleen cells to produce the same results. The implications of these findings are discussed.« less

Expression of Herpes Simplex Virus Type 1 (HSV-1) immediate early gene products has been bound to be sufficient for NK cell mediated lysis of HSV-1 infected FS. To block the targets at various stages in the infectious cycle, HSV-FS were irradiated with UV light for 1 min at 2, 6, and 20 hr post-infection. NK mediated lysis of 2 hr and 5 hr UV treated HSV-FS was 2-fold higher than non-UV treated HSV-FS despite a {gt}99% inhibition in virus yield. In contrast, 20 hr infected targets were lysed less well than 2 and 6 hr targets despite strong glycoprotein expressionmore » and induction of high levels of interferon-alpha (IFN-{alpha}) production by effector PBMC's; this lysis was not enhanced by UV treatment. Since NK lysis of HSV-FS has been found to be dependent on an HLA-DR{sup +} accessory cell (AC), lysis of irradiated HSV-FS by PBMC's depleted of AC was measured. Such depletion eradicated NK lysis of the UV treated HSV-FS indicating that irradiation does not overcome the AC requirement for NK lysis. UV irradiation of another HLA-DR{sup +} dependent target, Vesicular Stomatitis Virus (VSV) infected FS led to a dramatic reduction in both NK lysis and IFN-{alpha} induction. HSV-1 is a DNA virus whose genes are expressed in a cascade fashion whereas VSV is an RNA virus. The authors hypothesize that the enhancement in AC dependent NK activity observed for UV irradiated HSV-FS, but not VSV-FS, targets is due to overproduction of either a cellular or viral gene product which specifically occurs early in the HSV-1 infectious cycle and is downregulated by 20 hr post-infection.« less

In this report they present data on the spontaneous cytotoxic (NK) activity of scalded rat splenic lymphocytes. Sprague-Dawley rats (220-250 grams) were given 40% total body surface area full thickness burn injury by immersing the anesthetized rats in 90/sup 0/C water. Groups of rats were sacrificed at 1,2,4 and 7 day post burn (DPB). Splenic lymphocytes were tested for their ability to lyse YAC-1 target cells in a /sup 51/Cr release assay by incubating /sup 51/Cr-labelled YAC cells with lymphocytes at effector to target (E:T) ratios of 200:1 to 12:1. NK activity of the splenic lymphocytes from scalded rats wasmore » observed to be suppressed at all E:T ratios as early as 1 DPB. This decrease was observed at all time periods of study. Their present observations and previous findings of suppressed lymphoproliferative responses in scalded rats support similar findings in human studies, thereby making the rat a good model of immune function studies following thermal injury.« less